On March 26, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators will present at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 25-30, 2025 in Chicago, Illinois (Press release, Genprex, MAR 26, 2025, View Source [SID1234651458]). The collaborators will present positive preclinical data from a study of its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC).
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"We are delighted to have our academic partners present positive preclinical data on our lead drug candidate, REQORSA, as a potential therapeutic treatment for Ras inhibitor resistant lung cancer," said Ryan Confer, President and Chief Executive Officer at Genprex. "These preclinical data further validate REQORSA as a potential treatment for many types of cancer, including another subset of lung cancer. We remain highly encouraged by the role that TUSC2 plays in the treatment of lung cancer and by our preclinical programs expanding on the potential use of REQORSA to treat many types of cancer where patient populations continue to have unmet medical needs."
The featured Genprex-supported poster to be presented at AACR (Free AACR Whitepaper) 2025:
Title: Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance in Molecular Targeted Therapies 3
Session Date and Time: Tuesday, April 29 from 2-5 p.m. CT
Location: Poster Section 17
Poster Board Number: 12
Abstract Presentation Number: 5517
The featured Genprex-supported abstract to be presented at AACR (Free AACR Whitepaper) 2025:
Acquired resistance (AR) to Lumakras (sotorasib), the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant NSCLC. Despite initial responses, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms underlying AR include the emergence of additional mutations in the KRAS gene, reactivation of the KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene with immunogenic properties, exhibits multifunctional activity by inhibiting downstream signaling pathways, including MAPK and mTOR; arresting the growth and proliferation of cancer cells; inducing tumor cell death; and activating innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib AR in KRASG12C mutant NSCLC mouse xenografts.
The data indicate that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. Re-expression of TUSC2 into AR PDXOs significantly decreased the viability of organoids compared with the empty vector. The H23AR tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. However, treatment with REQORSA was highly effective in controlling tumor growth compared to treatment with sotorasib alone or the control groups. REQORSA alone also exhibited a strong antitumor effect on TC314AR PDXs. Sotorasib alone showed no significant antitumor activity in these models. However, a synergistic antitumor effect was observed when TC314AR PDX tumors were treated with the combination of REQORSA and sotorasib.
In conclusion, researchers demonstrated that REQORSA, alone or in combination with sotorasib, induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C mutant sotorasib-acquired resistant xenograft and PDX tumors.
About Reqorsa Gene Therapy
REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.